Alternative titles; symbols
HGNC Approved Gene Symbol: SPDEF
Cytogenetic location: 6p21.31 Genomic coordinates (GRCh38) : 6:34,537,802-34,556,329 (from NCBI)
PDEF is an ETS transcription factor expressed in prostate epithelial cells. It acts as an androgen-independent transactivator of PSA (176820) expression.
Oettgen et al. (2000) identified PDEF within an EST from a subtracted prostate benign hyperplasia cDNA library, and they obtained the full-length clone by RACE of an adult prostate cDNA library. The deduced 335-amino acid protein has a calculated molecular mass of 37.5 kD. PDEF contains 2 putative PEST sequences, one near the N terminus and the other at the center of the protein, a central pointed domain, which is characteristic of some ETS family members and weakly homologous to the SAM protein-protein interaction domain of polycomb proteins and Eph receptors, and an ETS DNA-binding domain. It also has several potential phosphorylation sites, including 8 mitogen-activated protein kinase (MAPK; see 602898) phosphorylation sites, 5 of which are clustered at the N terminus. Northern blot analysis detected a 2.0-kb transcript expressed almost exclusively in prostate gland. Low levels of PDEF were detected in ovary, mammary gland, and salivary gland. RT-PCR of several cell lines detected expression only in a prostate epithelial cancer cell line. In situ hybridization on frozen sections of prostate showed diffuse strong expression restricted to luminal epithelial cells.
Oettgen et al. (2000) determined that PDEF bound with high affinity to DNA containing sequences found in 2 of the 11 putative ETS-binding sites in the PSA promoter/enhancer region. PDEF is a unique ETS family member in that it showed highest affinity for GGAT rather than GGAA in the core of the binding site. Using a promoter-reporter construct cotransfected with PDEF into simian kidney cells, Oettgen et al. (2000) determined that PDEF is an androgen-independent transcriptional activator of the PSA promoter.
Park et al. (2007) showed that Spdef was expressed in a subset of epithelial cells in tracheal glands and in the conducting airways of fetal and adult mouse lung. Spdef directly interacted with Ttf1 (TITF1; 600635) and influenced expression of a number of genes in epithelial cells and conducting airways. Il13 (147683)- and Stat6 (601512)-dependent induction of Spdef was observed in association with goblet cell hyperplasia. Expression of Spdef in nonciliated airway epithelial cells (club cells) caused goblet cell hyperplasia, demonstrating its role in the regulation of airway epithelial differentiation.
Oettgen, P., Finger, E., Sun, Z., Akbarali, Y., Thamrongsak, U., Boltax, J., Grall, F., Dube, A., Weiss, A., Brown, L., Quinn, G., Kas, K., Endress, G., Kunsch, C., Libermann, T. A. PDEF, a novel prostate epithelium-specific Ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. J. Biol. Chem. 275: 1216-1225, 2000. [PubMed: 10625666] [Full Text: https://doi.org/10.1074/jbc.275.2.1216]
Park, K.-S., Korfhagen, T. R., Bruno, M. D., Kitzmiller, J. A., Wan, H., Wert, S. E., Hershey, G. K. K., Chen, G., Whitsett, J. A. SPDEF regulates goblet cell hyperplasia in the airway epithelium. J. Clin. Invest. 117: 978-988, 2007. [PubMed: 17347682] [Full Text: https://doi.org/10.1172/JCI29176]